Mupirocin or pseudomonic acid A is also known by its chemical name 9-[(E)-4-[(2S,3R,4R,5S)-3,4-dihydroxy-5-[[(2S,3S)-3-[(2S,3S)-3-hydroxybutan-2-yl]oxiran-2-yl]methyl]oxan-2-yl]-3-methylbut-2-enoyl]oxynonanoic acid and CAS No. 12650-69-0. Its chemical structure is:

Mupirocin is a antibiotic agent produced by fermentation of Pseudomonas fluorescens. Mupirocin is active against a wide range of gram-positive and certain gram-negative bacteria by the inhibition of bacterial protein synthesis by reversibly and specifically binding to bacterial isoleucyl transfer-RNA synthetase.
Mupirocin is currently marketed by Smithkline Beecham in the pharmaceutical form of an ointment, a cream, and a nasal oinment under the tradename of Bactroban. Bactroban is approved in the European Union (EU) and the United States of America as a topical antibiotic. In the EU, mupirocin is indicated for the treatment of acute primary bacterial skin infections, e.g. impetigo and folliculitis, and secondary bacterial skin infections, e.g. dermatitis, due to organisms which are sensitive to mupirocin.
Both topical compositions of Bactroban for use on the skin, i.e. Bactroban ointment and Bactroban cream, are formulated with hydrophilic ointment bases. Bactroban ointment is formulated with a water soluble ointment base which consists in a mixture of polyethyleneglycols and Bactroban Cream is formulated with a water-removable water in oil cream base.
Mupirocin and its commercial salts, e.g. mupirocin calcium, are mainly hydrophobic and, generally, mupirocin compositions which are based on hydrophilic bases or aqueous mediums tend to inestability.
Mupirocin has also been formulated with lipophilic bases. Unfortunately, they are not always suitable for dissolving mupirocin. Generally, dissolution of the active ingredient is more desirable than suspension to increase clinical effect of topical compositions. Dissolution improve the diffusion of the active ingredient from the composition to the treatment site. EP251434A2 discloses topical lipophilic ointments and water based creams of mupirocin and its calcium salt. As reported in the Examples, the lipophilic ointments provided were unable to dissolve more than 1% of the active ingredient in the composition.
Other compositions of mupirocin have also been disclosed in the art with the aim to improve mupirocin stability in the composition. For instance, EP1174133A1 discloses topical compositions based in the use of a hydrophobic phase, in particular a composition comprising amorphous mupirocin calcium, a hydrophobic phase, and hexylene glycol as solvent.
Although topical creams and ointments comprising an active ingredient are widely used, their utility decrease when the composition is required to stay in the site of treatment for a long time. The clinical effect of topical treatments are impaired because compositions are easily removed from the application site due to transpiration, humidity, and erosion, resulting in the need of increasing the daily applications of the composition in the treatment site and, thus, difficulting patient compliance of the treatment.
Bioadhesive and film-forming compositions, which remain in the site of treatment for longer time, have been developed to improve clinical effect of topical compositions and patient compliance. For instance, WO199823291A1 discloses general film-forming pharmaceutical compositions comprising delivery rate modulating polymers.
WO200410988A1 discloses aqueous compositions of mupirocin with ethylcellulose as a rate modulating hydrophobic polymer. Although, the disclosure is silent about the effects of mupirocin compositions disclosed, the skin permeation results provided for tretinoin compositions showed a noticeable delivery of the active ingredient through the epidermis and, therefore, making available the active ingredient sistemically. This is a disadvantage since permeation of topical drugs through the skin can modify the safety profiles of the pharmaceutical or veterinary product, a critical feature when assessing bioequivalence between a new composition of a marketed pharmaceutical or veterinary product.
Therefore, as extracted from the state of the art exposed above, it would be desirable to have at one's disposal improved stable topical pharmaceutical or veterinary compositions of mupirocin with improved clinical effect, while maintaining suitable safety profiles for assessing bioequivalence with commercial compositions of mupirocin.